Chemistry:1-Methyltryptamine

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1-Methyltryptamine (1-methyl-T, 1-MT or 1-Me-T; code name PAL-637) is a serotonin receptor agonist and monoamine releasing agent of the tryptamine family.[1][2][3] It is the 1-methyl derivative of tryptamine (T; PAL-235).[1][2][3]

The drug is known to act as a serotonin 5-HT2A receptor agonist (Ki = 473 nM; EC50 = 209–4,560 nM; Emax = 55–99%), as a serotonin releasing agent (EC50 = 53.1 nM), and to be inactive in inducing the release of norepinephrine and dopamine (EC50 = >10,000 nM).[1] Its activities at other serotonin receptors were not reported.[1][3] 1-Methyltryptamine shows dramatically reduced affinity and activational potency as well as reduced efficacy at the serotonin 5-HT2A receptor compared to tryptamine (which showed Ki = 13.1 nM; EC50 = 7.36–99 nM; Emax = 101–104%).[3][1] It also shows slightly reduced potency as a serotonin releasing agent and abolished activity as a releaser of norepinephrine and dopamine relative to tryptamine (which had EC50 = 32.6 nM, 716 nM, and 164 nM, respectively).[1]

Analogues of 1-methyltryptamine, like 1-methylserotonin and 1-iPr-5-MeO-T, have been studied.[4] Similarly to the case of 1-methyltryptamine contrasted with tryptamine, they show dramatically reduced affinities and activational potencies at the human serotonin 5-HT2A receptor relative to their 1-unsubstituted counterparts (serotonin and 5-methoxytryptamine, respectively).[4]

See also

References

  1. ↑ 1.0 1.1 1.2 1.3 1.4 1.5 "Alpha-ethyltryptamines as dual dopamine-serotonin releasers". Bioorganic & Medicinal Chemistry Letters 24 (19): 4754–4758. October 2014. doi:10.1016/j.bmcl.2014.07.062. PMID 25193229. PMC 4211607. https://www.researchgate.net/publication/265390792. 
  2. ↑ 2.0 2.1 "Serotonin 2A Receptor (5-HT2AR) Agonists: Psychedelics and Non-Hallucinogenic Analogues as Emerging Antidepressants". Chemical Reviews 124 (1): 124–163. January 2024. doi:10.1021/acs.chemrev.3c00375. PMID 38033123. "In addition to natural tryptamine psychedelics, numerous synthetic analogues have been reported. Compounds in Figure 5A show that, compared to the prototype tryptamine (9, Ki = 29.7 nM at h5-HT2AR, [125I]-DOI), methylation of the indole NH group slightly increases the binding affinity (1-Metryptamine, 10, Ki = 11.7 nM).136 The introduction of a methoxy group at position 5 also enhances binding affinity (11, 5-MeO-T, Ki = 1.34 nM), but a further alkylation of the indole NH with an isopropyl group almost abolished the binding affinity (12, 1-iPr-5-MeO-T, Ki = 494 nM).136". 
  3. ↑ 3.0 3.1 3.2 3.3 McCorvy JD (16 January 2013). Mapping the binding site of the 5-HT2A receptor using mutagenesis and ligand libraries: Insights into the molecular actions of psychedelics (Ph.D. thesis). Purdue University. Retrieved 12 March 2025 – via Purdue e-Pubs.
  4. ↑ 4.0 4.1 "Assessment of the roles of serines 5.43(239) and 5.46(242) for binding and potency of agonist ligands at the human serotonin 5-HT2A receptor". Molecular Pharmacology 72 (5): 1200–1209. November 2007. doi:10.1124/mol.107.039255. PMID 17715398. https://citeseerx.ist.psu.edu/document?repid=rep1&type=pdf&doi=f8f6db4f799a4e416aa2cc94665b10329ac6f5a8. 



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